Statistical Analysis
Analyses were conducted with SAS® software (version 9.4.). The primary
analysis was performed with the intention-to-treat (ITT) set, i.e. all
randomized patients who received at least one dose of IMP. The primary
endpoint was analysed using a logistic regression model with adjustments
for treatment, baseline fibrinogen levels (categorized as ≤ 2,
]2;3], ]3,4], > 4 g/L) and centre (23 centres that
enrolled less than 20 patients were pooled as one centre). The treatment
effect was estimated as an odds ratio (OR) along with its 95%
Confidence Interval (95%CI) and tested with the Wald test at the 0.05
significance level. An OR below 1 indicated a lower failure risk in the
fibrinogen group compared to the control group. Missing data were not
replaced in the primary analysis. Sensitivity analyses for handling
missing data were performed. Another supportive analysis was performed
on the per-protocol (PP) set.
Changes in plasma fibrinogen levels from IMP administration to 2 hours
(H2), 6 hours (H6) and 2 days (D2) were analysed in a Mixed Model for
Repeated Measurements (MMRM). For continuous secondary efficacy
endpoints, treatment groups were compared with a t-test or a Wilcoxon
test, and binary endpoints were compared with a Pearson Chi-square test
or a Fisher exact test. All p-values provided for secondary efficacy
endpoints are for exploratory purposes only. No adjustments were made
for multiple comparisons.